Gelatinase B participates in collagen II degradation and releases glycosylated remnant epitopes in rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune disease characterized by chronic inflammation of the joints. It is associated with the activation of autoreactive T-cells and with production of autoantibodies. The main auto-antigen is collagen type II, which is a major constituent of the cartilage in the joint. The inflammation causes cartilage degradation, hyperplasia of synovial membranes, accumulation of excessive synovial fluid, and, in the worst cases, bone erosion. The exact aetiology is not known, but it is clear that inflammatory reactions and auto-antibodies, which activate the complement cascade, are main causes of the cartilage degradation. Inhibition of inflammation by interference with some of the main pro-inflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-a) has proven to be beneficial and constitutes the basis of currently approved treatments. Matrix metalloproteinases are a family of neutral Zn2+-dependent endoproteases, which share a number of homologous domains (Nagase and Woessner, 1999). These domains are the Zn2+-containing active site, kept inactive by a propeptide in the pro-enzyme form, and a hemopexin domain (Fig. 1). The latter domain is present in most MMPs except for matrilysins (MMP-7 and -26) and cysteine-array MMP (CA-MMP or MMP-23). Several MMPs contain additional domains, such as a carboxyterminal membrane anchor in membrane-type MMPs (MT-MMPs), a fibronectin-like domain in gelatinases A and B (MMP-2 and -9), and a unique mucin-type domain in gelatinase B. The latter domain is often named collagen type